The main goal of this study is to establish an animal model which can be used to define age-deficits in bone activity at the cellular and molecular levels and to design and test the effectiveness of novel treatment procedures for osteoporosis. A minor bone injury, initiated by aspiration of bone marrow, induces rapid bone formation in the marrow cavity followed by resorption of newly synthesized bone. Changes in the expression of osteoblast-related genes as well as growth factor genes that are associated with bone formation and resorption are also noted and correlate with changes in bone histology. Using this bone injury model, we have demonstrated multiple deficits in old bone. These include reduced bone formation, insufficient number of osteoprogenitor cells and osteoblasts, impaired expression of matrix proteins and altered expression pattern of growth factors and cytokines in old bone. Currently, we are using this model to test the effectiveness of various interventions including growth factors, stem cell replacement and minocycline, an antibiotic with anticollagenase activity, in restoring the ability of old bone to maintain bone mass.